The invention relates to the preparation of 2,5-diazabicyclo[2.2.1]heptane intermediates of use in the preparation of antibiotic quinolones such as disclosed in U.S. Pat. No. 4,775,668.
A method for the synthesis of 2,5-diazabicyclo[2.2.1]heptanes is described in Portoghese et al, J. Org. Chem., 31, 1059 (1966). According to this method, hydroxy-L-proline is transformed into tritosylhydroxy-L-prolinol which is first reacted with benzylamine and then hydrogen iodide, phosphorus, and acetic acid to form 2-benzyl-2,5-diazabicyclo[2.2.1]heptane dihydroiodide. U.S. Pat. No. 3,947,445 follows a similar procedure and then converts the dihydroiodide through a three step procedure into 2-methyl-2,5-diazabicyclo[2.2.1]heptane.